Output

Settings

Unfavorable Outcome

TTP

Target Product Profile Decisions

Decision percentages when tau_MAV = tau_TV = 0.025
nk NO-GO Continue GO
Slope, %: -10%
20 0.44 0.56 0.00
30 0.60 0.40 0.00
40 0.72 0.28 0.00
60 1.00
80 1.00
Slope, %: 0%
20 0.22 0.76 0.02
30 0.32 0.65 0.03
40 0.41 0.56 0.03
60 0.55 0.43 0.02
80 0.69 0.28 0.03
Slope, %: 10%
20 0.08 0.83 0.09
30 0.12 0.76 0.12
40 0.15 0.69 0.16
60 0.35 0.24 0.41
80 0.41 0.07 0.52
Slope, %: 20%
20 0.02 0.73 0.25
30 0.03 0.61 0.36
40 0.03 0.51 0.46
60 0.04 0.05 0.91
80 0.02 0.00 0.98
Slope, %: 30%
20 0.01 0.49 0.50
30 0.00 0.36 0.63
40 0.00 0.22 0.78
60 0.00 1.00
80 1.00
Slope, %: 40%
20 0.00 0.29 0.71
30 0.00 0.12 0.88
40 0.04 0.96
60 1.00
80 1.00
When theta_mav = 0, theta_TV = 20, tau_mav = tau_TV = 0.025.

When theta_mav = 0, theta_TV = 20, tau_mav = tau_TV = 0.025.

Ranking

\(\psi_1\): Comparing Against Control

\(f(\psi_2)\): Comparing estimated confidence in top 2 regimens

\(\psi_3\): Posterior probability of ranking in top 2

Together

New Attempt

2 Winners

Sub-optimal relapse rate (10%).
true.slope nk Criterion NO-GO Continue GO
Relative TTP slope: -10%
-10% 20 other 18 (1.8) 547 (54.7)
-10% 20 Unfavorable outcome only 17 (1.7)
-10% 20 TPP only 418 (41.8)
-10% 30 other 122 (12.2) 314 (31.4)
-10% 30 Unfavorable outcome only 83 (8.3)
-10% 30 TPP only 481 (48.1)
-10% 40 other 386 (38.6) 149 (14.9)
-10% 40 Unfavorable outcome only 131 (13.1)
-10% 40 TPP only 334 (33.4)
Relative TTP slope: 10%
10% 20 other 3 (0.3) 848 (84.8) 35 (3.5)
10% 20 Unfavorable outcome only 32 (3.2)
10% 20 TPP only 82 (8.2)
10% 30 other 20 (2) 681 (68.1) 22 (2.2)
10% 30 Unfavorable outcome only 185 (18.5)
10% 30 TPP only 92 (9.2)
10% 40 other 86 (8.6) 428 (42.8) 5 (0.5)
10% 40 Unfavorable outcome only 431 (43.1)
10% 40 TPP only 50 (5)
Relative TTP slope: 35%
35% 20 Unfavorable outcome only 35 (3.5)
35% 20 other 369 (36.9) 596 (59.6)
35% 30 Unfavorable outcome only 205 (20.5)
35% 30 TPP only 2 (0.2)
35% 30 other 177 (17.7) 616 (61.6)
35% 40 Unfavorable outcome only 517 (51.7)
35% 40 other 44 (4.4) 439 (43.9)
Relative TTP slope: 40%
40% 20 Unfavorable outcome only 35 (3.5)
40% 20 TPP only 3 (0.3)
40% 20 other 289 (28.9) 673 (67.3)
40% 30 Unfavorable outcome only 205 (20.5)
40% 30 TPP only 1 (0.1)
40% 30 other 98 (9.8) 696 (69.6)
40% 40 Unfavorable outcome only 517 (51.7)
40% 40 other 12 (1.2) 471 (47.1)
true.slope nk decision decision2 n prop
-10% 20 NO-GO Unfavorable outcome only 3 0.003
-10% 20 NO-GO TPP only 436 0.436
-10% 20 Continue other 561 0.561
-10% 30 NO-GO other 24 0.024
-10% 30 NO-GO Unfavorable outcome only 10 0.010
-10% 30 NO-GO TPP only 579 0.579
-10% 30 Continue other 387 0.387
-10% 40 NO-GO other 58 0.058
-10% 40 NO-GO Unfavorable outcome only 17 0.017
-10% 40 NO-GO TPP only 662 0.662
-10% 40 Continue other 263 0.263
10% 20 NO-GO Unfavorable outcome only 3 0.003
10% 20 NO-GO TPP only 85 0.085
10% 20 Continue other 876 0.876
10% 20 GO other 36 0.036
10% 30 NO-GO other 4 0.004
10% 30 NO-GO Unfavorable outcome only 30 0.030
10% 30 NO-GO TPP only 108 0.108
10% 30 Continue other 833 0.833
10% 30 GO other 25 0.025
10% 40 NO-GO other 13 0.013
10% 40 NO-GO Unfavorable outcome only 62 0.062
10% 40 NO-GO TPP only 123 0.123
10% 40 Continue other 791 0.791
10% 40 GO other 11 0.011
35% 20 NO-GO Unfavorable outcome only 3 0.003
35% 20 Continue other 381 0.381
35% 20 GO other 616 0.616
35% 30 NO-GO Unfavorable outcome only 34 0.034
35% 30 NO-GO TPP only 2 0.002
35% 30 Continue other 220 0.220
35% 30 GO other 744 0.744
35% 40 NO-GO Unfavorable outcome only 75 0.075
35% 40 Continue other 84 0.084
35% 40 GO other 841 0.841
40% 20 NO-GO Unfavorable outcome only 3 0.003
40% 20 NO-GO TPP only 3 0.003
40% 20 Continue other 298 0.298
40% 20 GO other 696 0.696
40% 30 NO-GO Unfavorable outcome only 34 0.034
40% 30 NO-GO TPP only 1 0.001
40% 30 Continue other 113 0.113
40% 30 GO other 852 0.852
40% 40 NO-GO Unfavorable outcome only 75 0.075
40% 40 Continue other 36 0.036
40% 40 GO other 889 0.889
Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the `2 Winners` simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the 2 Winners simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

1 Winner

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the `1 Winner` simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the 1 Winner simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

4 Winners

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the `4 Winners` simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the 4 Winners simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

No Winners

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the `No Winners` simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

Interim analysis decision probabilities for simulated arms with TTP slope relative to the control as specified in the panels (all corresponding to the No Winners simulation setting) and unfavorable outcome rates of A) 10% (unfavorable), B) 5% (minimal), and C) 2.5% (desirable). Arms are flagged for a GO decision if they meet all the following conditions: fewer than 2 unfavorable outcomes, evidence of meeting the target product profile, and a posterior probability greater than 50% of ranking in the top two arms. A pattern is applied to differentiate the criterion responsible for NO-GO decisions. Arms are flagged for a NO-GO decision if they experience any of the following conditions: 2 or more unfavorable outcomes (stripes), do not have evidence of meeting the target product profile (dots), or meet both conditions (plain). All arms that do not meet the criteria for a GO or NO-GO decision, receive a “Continue” designation. Results are based on 1,000 simulated datasets per setting.

Single Example

Interim results from a single simulated phase 2B study with thirty partients per regimen. The target product profile (TPP) assumes \(\theta_{MAV} = 0, \theta_{TV} = 20, \tau_{MAV} = \tau_{TV} = 0.025\).
Interim 1
Regimen Duration No. patients No. relapses \(\hat{\theta}_{0.5}\) \(\hat{\theta}_{0.025}\) \(\hat{\theta}_{0.975}\) \(P(\theta_k > \theta_{MAV})\) \(P(\theta_k > \theta_{TV})\) TPP decision \(\hat{\psi}_1\) \(\hat{\psi}_2\) \(\hat{\psi}_3\)
1 26 30 0 0.000 0.022
2 16 30 1 0.111 -0.129 0.422 0.808 0.263 Continue 0.808 0.001 0.026
3 16 30 0 0.233 -0.012 0.569 0.966 0.588 Continue 0.966 0.004 0.240
4 16 30 0 0.319 0.054 0.688 0.991 0.790 GO 0.991 0.048 0.715
5 16 30 0 0.556 0.257 0.950 1.000 0.993 GO 1.000 0.947 0.997